Abstract 4202: A novel 3D model investigating the pathophysiology of prostate cancer bone marrow metastasis

Abstract

Abstract Our study is aimed to apply a 3-dimensional (3-D) in vitro model emulating the extracellular matrix (ECM) of the bone marrow microenvironment (BMM) to explore the interaction of disseminated Prostate Cancer (PC) cells and ECM. Wharton's Jelly (WJ), which histologically and biochemically resembles the ECM part of the hematopoietic stem cell (HSC) niche, was decellularized as a novel 3-D culture platform, named as decellularized WJ matrix (DWJM). CD133, a critical marker of PC stem cells (PCSC), was chosen to initially evaluate the PCSC phenotype of DU-145 cells cultured using DWJM by flow cytometry and Image-Stream. DWJM was used to culture PC Cell line DU-145 cells. Enriched CD133(+) cells by Fluorescence-Activated Cell Sorting (FACS) were further analyzed for functional phenotypes of PCSC, and the mechanism of reactivated expression of CD133 was also investigated. A small percentage (about 2-5%) of CD133(+) DU-145 cells were detected after DU-145 cell culturing using DWJM for 3-7 days. Sorted CD133+ cells formed more colonies in vitro and manifested some characteristics of Epithelial-to-Mesenchymal Transition (EMT), including increased nuclear to cytoplasmic ratio and spindle-cell morphology. The undetectable expression of CD133 mRNA and protein in parental DU-145 cells was at least partly caused by promotor methylation, while culturing using DWJM reactivated the expression of CD133 by demethylating the CD133 DNA promotor. Taken together, our in vitro findings provide preliminary findings to support the possible conversion of disseminated PC cells to PCSC by epigenetic modulation in the BMM, and these early findings warrant further validation using an in vivo mouse model. Citation Format: Jianhui Yang. A novel 3D model investigating the pathophysiology of prostate cancer bone marrow metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4202.